Update: Aktuelle klinische Entwicklungen bei pulmonaler Hypertonie

Zusammenfassung

Die therapeutischen Möglichkeiten bei Patienten mit Lungenhochdruck haben sich in den letzten Jahren deutlich verbessert. Jedoch muss bei jedem Patienten vor Einleitung einer Therapie eine ätiologische Zuordnung erfolgen. Die pulmonale arterielle Hypertonie (PAH; Gruppe 1 der Venedig-Klassifikation) ist von anderen Formen der pulmonalen Hypertonie (PH; Gruppen 2 – 5 der Venedig-Klassifikation) klar abzugrenzen. Zur Behandlung der PAH stehen mit Prostazyklin-Analoga (Prostanoide), Endothelin-Rezeptor-Antagonisten (ERA) und Phosphodiesterase-5-Inhibitoren mittlerweile Pharmaka aus drei verschiedenen Substanzklassen zur Verfügung, für die jeweils ein Wirksamkeitsnachweis erbracht wurde. Eine aktuelle Metaanalyse zeigt, dass durch diese Therapien erstaunlicherweise bereits innerhalb kurzer Beobachtungszeiträume eine Verbesserung der Überlebensrate erzielt werden kann. Dennoch weisen viele Patienten weiterhin eine erhebliche klinische Symptomatik und eine deutlich eingeschränkte Lebenserwartung auf. Im Folgenden soll ein Überblick über die aktuellen Entwicklungen bei zugelassenen Therapien der PAH, bei der Etablierung neuer Therapiekonzepte zur Behandlung der PAH, sowie zu den Therapiemöglichkeiten bei anderen Formen der PH gegeben werden.

Summary

During the last years, therapeutic options for the treatment of pulmonary arterial hypertension (PAH) have significantly improved. However, the therapeutic concept depends on the etiology of the disease, so that an exact classification is mandatory. Currently, three substance classes are approved for the treatment of PAH (Group I of the Venice Classification): Endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, and prostanoids. After the World Conference in Dana Point (2008), recent changes in therapeutic strategies comprise the early treatment of the disease, as well as the increased importance of an early use of combination therapy if treatment goals are not met. Several new substances are currently evaluated in clinical trials. The soluble guanylate cyclase (sGC) stimulators achieve potent, NO-independent vasodilation. Another promising pathophysiological approach is currently evaluated by the use of tyrosine kinase inhibitors – anti-proliferative drugs which inhibit or even may reverse the pulmonary vascular remodeling process. Serotonin receptor antagonists are also reported to have anti-proliferative, anti-thrombotic and anti-fibrotic effects. Other forms of pulmonary hypertension (Groups II-V) are strictly separated from PAH. Evidence on treatment with PAH specific agents is strongly needed for these groups. Patients with non-PAH pulmonary hypertension should be referred to PAH expert centers, and preferably treated in controlled studies.

Schlüsselwörter

pulmonale arterielle Hypertonie - Tyrosinkinasen - Platelet-derived Growth Factor (PDGF) - sGC-Stimulator - Serotonin

Keywords

pulmonary arterial hypertension - tyrosine kinase - platelet-derived growthfactor (PDGF) - sGC stimulator - serotonin

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